MRTX1133|cas:2621928-55-8|西域试剂

MRTX1133,99.42%

产品编号：Bellancom-134813| CAS NO：2621928-55-8| 分子式：C₃₃H₃₁F₃N₆O₂| 分子量：600.63

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货号	价格	库存与货期
Bellancom-134813	￥5100.00	杭州北京（现货）
Bellancom-134813	￥7800.00	杭州北京（现货）
Bellancom-134813	￥14000.00	杭州北京（现货）

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MRTX1133

产品介绍

MRTX1133 是一种非共价、强效和选择性 KRAS G12D 抑制剂。MRTX1133 以最佳方式填充开关 II 口袋，并延伸三个取代基以与蛋白质良好地相互作用，对 KRAS G12D 的 K_D 为 0.2 pM。MRTX1133 阻止 SOS1 催化的核苷酸交换和/或KRAS G12D/GTP/RAF1 复合物的形成，从而抑制突变体 KRAS 依赖性信号转导。MRTX1133 选择性抑制 KRAS G12D 突变体肿瘤细胞，但不抑制 KRAS 野生型细胞。MRTX1133 在细胞实验中具有一位数纳摩尔活性，在含有 KRAS G12D 突变的肿瘤模型中具有显著的体内疗效。

生物活性

MRTX1133 is a noncovalent, potent, and selective KRAS G12D inhibitor. MRTX1133 optimally fills the switch II pocket and extends three substituents to favorably interact with the protein, resulting in an estimated K_D against KRAS G12D of 0.2 pM. MRTX1133 prevents SOS1-catalyzed nucleotide exchange and/or formation of the KRAS G12D/GTP/RAF1 complex, thereby inhibiting mutant KRAS-dependent signal transduction. MRTX1133 selectively inhibits KRAS G12D mutant, but not KRAS wild-type, tumor cells. MRTX1133 has single digit nanomolar activity in cellular assays and marked in vivo efficacy in tumor models harboring KRAS G12D mutations.

体外研究

MRTX1133 inhibits ERK phosphorylation in the AGS cell line with an IC₅₀ ranging 1-10 nM (AsPC-1, Panc 04.03, Panc 02.03, SW1990, GP2D, Suit2, A427, SNU1033, and HPAC cells). In a 2D viability assay, the IC₅₀ of MRTX1133 is 6 nM against AGS cells (KRAS G12D), while demonstrating more than 500-fold selectivity against MKN1, a cell line which is dependent on KRAS for its growth and survival due to the amplification of wild-type KRAS.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

体内研究

MRTX1133 displays efficacious in a KRAS G12D mutant xenograft mouse tumor model.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	6-8-weekold, female, athymic nude-Foxn1^nu mice (Panc 04.03 model)
Dosage:	3, 10, or 30 mg/kg
Administration:	Intraperitoneal; twice a day for 28 days
Result:	An antitumor efficacy study in this model resulted in MRTX1133 dose-dependent antitumor activity with 94% growth inhibition observed at 3 mg/kg BID (IP) and tumor regressions of -62% and -73% observed at 10 and 30 mg/kg BID (IP), respectively.

体内研究

MRTX1133 displays efficacious in a KRAS G12D mutant xenograft mouse tumor model.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	6-8-weekold, female, athymic nude-Foxn1^nu mice (Panc 04.03 model)
Dosage:	3, 10, or 30 mg/kg
Administration:	Intraperitoneal; twice a day for 28 days
Result:	An antitumor efficacy study in this model resulted in MRTX1133 dose-dependent antitumor activity with 94% growth inhibition observed at 3 mg/kg BID (IP) and tumor regressions of -62% and -73% observed at 10 and 30 mg/kg BID (IP), respectively.

性状

Solid

溶解性数据

In Vitro:

DMSO : 50 mg/mL (83.25 mM; Need ultrasonic)

配制储备液

浓度溶剂体积质量	1 mg	5 mg	10 mg

1 mM	1.6649 mL	8.3246 mL	16.6492 mL
5 mM	0.3330 mL	1.6649 mL	3.3298 mL
10 mM	0.1665 mL	0.8325 mL	1.6649 mL

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

1.

请依序添加每种溶剂： 10% SBE-β-CD/50 mM citrate pH 5.0
Solubility: 10 mg/mL (16.65 mM); Clear solution; Need ultrasonic and warming and adjust pH to 5 with HCl and heat to 60°C
2.

请依序添加每种溶剂： 10% DMSO 90% (20% SBE-β-CD in saline)
Solubility: 3.5 mg/mL (5.83 mM); Suspended solution; Need ultrasonic

此方案可获得 3.5 mg/mL (5.83 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。
以 1 mL 工作液为例，取 100 μL 35.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。
将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
3.

请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% saline
Solubility: ≥ 2.5 mg/mL (4.16 mM); Clear solution

此方案可获得 ≥ 2.5 mg/mL (4.16 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。
将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液